Arteriolar niches maintain haematopoietic stem cell quiescence
Yuya Kunisaki,
Ingmar Bruns,
Christoph Scheiermann,
Jalal Ahmed,
Sandra Pinho,
Dachuan Zhang,
Toshihide Mizoguchi,
Qiaozhi Wei,
Daniel Lucas,
Keisuke Ito,
Jessica C. Mar,
Aviv Bergman and
Paul S. Frenette ()
Additional contact information
Yuya Kunisaki: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine
Ingmar Bruns: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine
Christoph Scheiermann: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine
Jalal Ahmed: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine
Sandra Pinho: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine
Dachuan Zhang: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine
Toshihide Mizoguchi: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine
Qiaozhi Wei: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine
Daniel Lucas: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine
Keisuke Ito: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine
Jessica C. Mar: Albert Einstein College of Medicine
Aviv Bergman: Albert Einstein College of Medicine
Paul S. Frenette: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine
Nature, 2013, vol. 502, issue 7473, 637-643
Abstract:
Abstract Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant three-dimensional associations in the mouse bone marrow among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal bone marrow. These arterioles are ensheathed exclusively by rare NG2 (also known as CSPG4)+ pericytes, distinct from sinusoid-associated leptin receptor (LEPR)+ cells. Pharmacological or genetic activation of the HSC cell cycle alters the distribution of HSCs from NG2+ periarteriolar niches to LEPR+ perisinusoidal niches. Conditional depletion of NG2+ cells induces HSC cycling and reduces functional long-term repopulating HSCs in the bone marrow. These results thus indicate that arteriolar niches are indispensable for maintaining HSC quiescence.
Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:502:y:2013:i:7473:d:10.1038_nature12612
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DOI: 10.1038/nature12612
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